DESCRIPTION: Peripheral sensory motor neuropathy is a common complication of diabetes and eventually occurs in more than 66 percent of diabetics. Changes in quantitative measures in nerve functions and nerve morphometry have never been convincingly correlated with improved clinical outcome. In addition, there is little history data on the morphologic and morphometric changes over the time in human nerve in the presence of diabetes in large part due to the invasive nature of sural nerve biopsy which is traditionally used to evaluate the neuropathy in diabetes. The recent identification of a specific neural protein and the commercial availability of antibodies to this protein (PGP 9.5) as well as standardized, reproducible counting techniques present the opportunity to use a simple skin punch biopsy technique in a diabetic population to investigate morphometric and morphologic changes in neuropathy. Initially, normal ranges for non-diabetics will be established then cutaneous nerve morphometric and morphologic changes in diabetes will be correlated with stage of neuropathy in sural nerve biopsy results. This simple procedure in staining technique will facilitate the study of the natural history and physiologic and anatomic alterations that occur with diabetic neuropathy in evaluation of potential therapies. Skin biopsies are relatively painless, carry minimal morbidity, and can be performed at several different anatomic sites to demonstrate regionally variation in the severity of neuropathy, and importantly, can be repeated longitudinally to track the progression of diabetic neuropathy and thus can be used to assess the efficacy of the treatment. Thus, this technique would provide a valuable biologic marker and a substitute for a much more invasive and more expensive sural nerve biopsy to be used in studies of diabetic peripheral neuropathy.